Alcohol accounts for major disability worldwide and available treatments are insufficient. A massive growth in the area of addiction neuroscience over the last several decades has not resulted in a corresponding expansion of treatment options available to patients. In this chapter, we describe our experience with building translational research pro...
Published in Psychopharmacology
RationaleThe abuse potential of opioids may be due to their reinforcing and rewarding effects, which may be attenuated by neurokinin-1 receptor (NK1R) antagonists.ObjectiveThis study was conducted to measure the effects of opioid and NK1R blockade on the potentiation of brain stimulation reward (BSR) by morphine using the intracranial self-stimulat...
Published in Psychopharmacology
RationaleGenetic inactivation or pharmacological antagonism of neurokinin 1 (NK1) receptors blocks morphine and alcohol reward in rodents, while NK1 antagonism decreases alcohol craving in humans. The role of the NK1 system for relapse-like behavior has not previously been examined.ObjectiveDivergence between human and rodent NK1 receptors has limi...
Published in Neuropharmacology
The tachykinin NK(3) receptor shows promise as a novel target for antipsychotics, but knowledge of downstream activity following tachykinin NK(3) receptor activation is lacking. To determine the practical utility of senktide-induced tail whips in mice as a tool for determining and characterizing downstream activity following tachykinin NK(3) recept...
Published in Peptides
Neuropeptides related to vertebrate tachykinins have been identified in Drosophila and are referred to as drosotachykinins, or DTKs. Two Drosophila G protein-coupled receptors, designated NKD (neurokinin receptor from Drosophila; CG6515) and DTKR (Drosophila tachykinin receptor; CG7887), display sequence similarities to mammalian tachykinin recepto...
Published in Bioorganic & medicinal chemistry letters
Lead optimisation starting from the previously reported selective quinoline NK(3) receptor antagonists talnetant 2 (SB-223412) and 3 (SB-222200) led to the identification of 3-aminoquinoline NK(3) antagonist 10 (GSK172981) with excellent CNS penetration. Investigation of a structurally related series of sulfonamides with reduced lipophilicity led t...
Published in Encyclopedia of Basic Epilepsy Research
There are at least seven tachykinins in the human body, and their actions are diverse. Tachykinins are predominantly excitatory, in the brain (presynaptic enhancement of glutamate release), and enhance motility in the gut and inflammation in many tissues. Substance P and neurokinin B are involved in status epilepticus, and are overexpressed in the ...
Published in Neuroendocrinology
The pars tuberalis (PT) is a distinct subdivision of the anterior pituitary gland that plays a central role in regulating seasonal prolactin release. In sheep, there is compelling evidence that seasonal changes in light, transformed into a melatonin signal, are interpreted by the PT to modulate the release of a factor which affects prolactin releas...
Published in Psychopharmacology
RationaleThe neurokinin 3 (NK3) receptor is a novel target under investigation for improvement of the symptoms of schizophrenia due to its ability to modulate dopaminergic signaling. However, research on effects of NK3 antagonism with animal models has been hindered because of species differences in the receptor between humans, rats, and mice.Objec...
Published in Biochemical and Biophysical Research Communications
Amphiphilic peptides with positive charges such as substance P (SP) and mastoparan (MP) are known to induce exocytosis in rat peritoneal mast cells. To elucidate whether and how intracellular Ca 2+ signaling is involved in the peptide-induced exocytosis, here we investigated the relationships between an increase in intracellular free Ca 2+ concentr...
